TopoTarget A/S
Symbion
Fruebjergvej 3
DK 2100 Copenhagen
Denmark
Tel: +45 39 17 83 92
Fax: +45 39 17 94 92
CVR-nr: 25695771
www.topotarget.com
Interim report
for the nine months ended 30 September 2007
Highlights from Q3 2007
• Additional evidence of clinical efficacy of belinostat was announced after
the end of Q3 where encouraging data in solid tumours were published.
Belino-stat is the company's lead late stage product candidate and a total of
15 tri-als ongoing
• Totect™ approved for sale on the US market by the US Food and Drug
Ad-ministration (FDA)
• Sales of Savene™ in Q3 amounted to DKK 4.6 million (approximately EUR 0.6
million)
• Two TopoTarget product candidates (APO866 & belinostat) included in Windhover
Information's international top 10 list of most interesting oncol-ogy projects
for partnering opportunities
• TopoTarget named in Ernst and Young's Top 10 most innovative biotech
companies in Europe published by Mandag Morgen magazine
• Operating loss amounted to DKK 160.9 million (approximately EUR 21.6 million)
against a loss of DKK 128.3 million (approximately EUR 17.2 mil-lion) in the
same period in the previous year
• Loss before tax of DKK 156.6 million (approximately EUR 21.0 million), as
compared to a loss of DKK 124.5 million (approximately EUR 16.7 million) in the
same period of last year
• Loss after tax of DKK 155.3 million (approximately EUR 20.9 million), as
compared to a loss of DKK 122.8 million (approximately EUR 16.5 million) in the
same period of last year. This corresponds to DKK (3.02) per share compared to
DKK (3.02) last year
• Pre tax loss guidance is changed to a range of DKK 255-275 million com-pared
to guidance on pre tax loss given in H1 2007 of DKK 275-295 million, primarily
due to positive synergies resulting from the integration of Apoxis S.A.
• Successful integration of Apoxis S.A. (TopoTarget Switzerland S.A.)
A conference call on the results for the first nine months of 2007 will be
hosted today, Wednesday 7 November 2007, at 15:00 (CET). Further in-formation
is contained in this announcement.
Interim report
for the nine months ended 30 September 2007
Copenhagen, Denmark - 7 November 2007 - The Board of Directors of TopoTarget
A/S (OMX: TOPO) today adopted the company's interim report for the nine months
ended 30 September 2007.
During the nine months period ended 30 September 2007, operating expenses
amounted to DKK 195.4 million against DKK 149.6 million in the year-earlier
period, primarily due to the establishment of Savene™ sales forces in Europe
and the US and the acquisition of Apoxis S.A. The operating loss for the
period was DKK 160.9 million, compared with DKK 128.3 million in the same
period of last year. The company posted a loss before tax of DKK 156.6 million
in the first nine months of 2007 against a pre-tax loss of DKK 124.5 million in
the same period of 2006. Cash, cash equivalents and marketable securities
amounted to DKK 463.1 million at 30 September 2007.
Milestones met during Q3 2007
• Initiated Phase I/II study with belinostat combination therapy for the
treat-ment of acute Myeloid Leukemia
• On 6 September TopoTarget received approval from the US FDA for Totect™ for
sale on the US market
• The integration of Apoxis S.A. took place, following the acquisition of the
Swiss biotech company at the end of Q2. TopoTarget's clinical pipeline has
accordingly been expanded with two promising anti-cancer compounds
re-spectively in phase I and II trials
Highlights for the period after 30 September 2007
• Belinostat positive clinical trial data published at the AACR-NCI-EORTC 2007
International Conference on Molecular Targets and cancer Therapeutics
• Significant anti tumour activity shown in Phase II study of belinostat in
combination with carboplatin and paclitaxel (BelCaP) treating patients with
relapsed ovarian cancer. Neil J. Finkler, MD, FACOG, FACS, Investi-gator and
Director of the Gynecologic Oncology Program at Florida Hos-pital Cancer
Institute in Orlando has said: “We are very encouraged by the level of activity
we have seen with BelCaP for the treatment of re-lapsed ovarian cancer,
including activity against platinum resistant tu-mors. We look forward to
continuing to treat those patients currently on study and further defining the
efficacy of BelCaP in the treatment of this disease.”
• National Cancer Institute (NCI) sponsored Phase II study using belino-stat as
monotherapy treating two types of ovarian cancer showed evi-dence of activity
and that the treatment were safe and well-tolerated in both patient populations
• Phase I study using oral belinostat treating patients with advanced solid
tumours showed compound to be safe and well-tolerated in doses that may provide
flexibility to complement the IV formulation of belinostat currently in Phase
II development
• NCI sponsored Phase I study using belinostat in combination with bor-tezomib
(Velcade®) treating patients with advanced solid tumours and lymphoma showed
the treatment to be well-tolerated in doses up to 600 mg/m2 belinostat and 1.3
mg/m2 bortezomib
• Totect™ launch in the US began positively and in accordance with our
ex-pectations with the first anthracycline extravasation kits shipped to our
dis-tributor 16 October 2007. The reception in the market has been positive as
the standard of care has been changed as Totect™ is the first and only
an-thracycline extravasation treatment approved in the US. Ten oncology
spe-cialists are working with their healthcare providers to provide educational
programs to the cancer infusion centers and institutions to build awareness of
Totect™ availability
• Siramesine: TopoTarget signed agreement with Lundbeck for worldwide rights in
cancer indications
Expected key milestones for the remainder of 2007
• Announcement regarding regulatory strategy for belinostat
• TopoTarget/CuraGen and the NCI have 15 ongoing studies with belinostat.
Results from a Phase II study in cutaneous T-Cell Lymphoma (CTCL) and
Peripheral T-Cell Lymphoma (PTCL) expected at the American Society of
Hematology (ASH) Annual Meeting in December 2007
• Launch of Savene™ in additional European countries
• Results from Baceca® Phase II trial
• Initial results from Savicol™ Phase II trial
Belinostat status
Belinostat (PXD101) - is an IV and oral class I and II HDAC inhibitor for the
treatment of both solid tumors and haematological malignancies. Belinostat is
TopoTarget's lead clinical candidate.
Intravenously and orally administered belinostat is currently evaluated in 15
clinical studies run by TopoTarget, CuraGen, and the National Cancer Institute
(NCI), USA. In the reporting period one clinical trial was initiated and one
was discontinued.
T-Cell Lymphoma
• Positive interim clinical response data showing proof-of-concept for
belinostat monotherapy have previously been reported for cutaneous T-Cell
Lymphoma (CTCL) and Peripheral T-Cell Lymphoma (PTCL). Up-dated clinical
results from an ongoing phase II study targeted to recruit a total of 68
patients diagnosed with T-Cell Lymphoma will be presented at the coming ASH
meeting in Atlanta (Monday 10 December, abstract 3453, poster board 2607)
Ovarian cancer
• A phase Ib trial of belinostat in combination with carboplatin and
pacli-taxel (BelCaP) presented at ASCO 2007 has shown this combination, in
heavily pre-treated patients, to be well-tolerated and clinically active
(RECIST/CA125 responses in pancreatic, rectal and ovarian cancer, and multiple
long-term stabilizations including treatment durations of ≥ 1 year in bladder
cancer, carcinoma of unknown primary, and melanoma). The BelCaP regimen is
currently further evaluated in patients with ovar-ian cancer and transitional
cell cancer of the bladder.
After the reporting period positive results from a phase II multicenter trial
of BelCaP for women with relapsed ovarian cancer were presented at the
AACR-NCI-EORTC meeting in San Francisco, 22-26 October. The data showed BelCaP
to be well-tolerated and 15 out of 16 evaluable pa-tients experienced reduction
in tumour size as measured by radiologic assessment. The study has progressed
to stage II in the Simon two-stage design based on three objective responses
among the initial pa-tients recruited. In addition, data from a NCI-sponsored
Phase II trial evaluating the activity of IV belinostat monotherapy in two
ovarian tu-mour populations (pre-treated with up to three prior chemotherapies)
was also presented at the AACR-NCI-EORTC meeting. To date a total of 12
patients with micropapillary/borderline (LMP) ovarian tumours have been
treated, including one patient achieving a partial response, and one showing a
CA125 response. In addition, nine patients achieved stabilization of disease.
In 18 patients with epithelial ovarian cancers (recurrent platinum resistant)
nine patients achieved stabilization of dis-ease, five had progressive disease,
and four were non-evaluable. Intra-venously administered belinostat was
considered safe and generally well-tolerated in these two ovarian tumour
populations.
Phase I data presented at AACR-NCI-EORTC meeting in San Francisco, 22-26
October 2007
• Initial tolerability and pharmacokinetic data from a large phase I study of
orally administered belinostat in patients with advanced solid tumours was
presented showing belinostat to be safe and well-tolerated includ-ing a
thorough evaluation of cardiac safety (no grade 3 or 4 QTc changes noted in
more than 2400 ECGs). Currently more than 60 pa-tients have been dosed in
sequential cohorts evaluating four schedules: once (QD) or twice (BID) daily
with continuous dosing, and QD or BID with dosing days 1 to 14 in a 3-weekly
cycle. The maximum tolerated dose (MTD) for continuous dosing has been
determined to be 250 mg twice daily. The MTD for the day 1 to 14 in a 21 day
cycle has not been reached and no DLT's (Dose Limiting Toxicity) were observed
in the 1000 mg QD cohort. Higher dose cohorts are now evaluated. Up until now
25% of treated patients have achieved stabilisation of disease for greater or
equal to 12 weeks (tumour reductions have not yet reached RECIST defined
criteria). Investigators concluded that oral belinostat has been safe and
well-tolerated at doses that may provide flexibility to complement the
intravenous formulation of belinostat which is currently in Phase II
development.
• Data from an NCI-sponsored phase I trial of intravenously administered
belinostat in combination with bortezomib in patients with advanced solid
tumours and lymphoma refractory to standard therapies or where no standard
treatment exists was also presented. Based on 17 patients (14 evaluable) the
investigators concluded that intravenous belinostat and bortezomib were
well-tolerated in combination at doses up to 600 mg/m2 belinostat and 1.3 mg/m2
bortezomib, with ongoing enrolment of patients into this dosing cohort. The
anti-tumour activity observed with the combination in this Phase I population
includes one patient with Ewing's Sarcoma that has maintained stable disease
(SD) for 4 cycles, and two patients, on with peritoneal and one with
appendiceal carci-noma, that have maintained SD for 3 cycles. Adverse events
were gen-erally grades 1-2 and reversible. No grade 4 non-haematologic
toxicities were reported.
Savene™/Totect™ status
TopoTarget's first product, Savene™/Totect™, is for the prevention of severe
tissue damage caused by anthracycline extravasation. Savene™ was launched in
October 2006 in selected European countries. Totect™ was approved by the US FDA
on 6 September 2007 and was launched on the US market on 16 Octo-ber 2007.
Launch and commercial activities of Savene™ in Europe and Totect™ in the US are
moving forward according to plan. The US market process to build aware-ness
continues and the sales expectations in the plan based on the anticipated
second half launch are maintained. In Europe TopoTarget continues to expand
into new markets and during July the company entered into an agreement with
Grupo Ferrer to market Savene™ in Spain and Portugal. An agreement was
finalized with BioPro to enter the Asian markets including China and Korea. The
company is also in late stage price negotiation discussions with the view to
ex-panding into Canada, France, and Italy.
Sales in the Nordic region and Benelux countries have exceeded the company's
initial expectations. TopoTarget has restructured its sales organisation in the
United Kingdom and in Germany in an effort to optimise sales efforts and learn
from successes. As part of TopoTarget's ongoing plan to streamline the
company's sales and marketing structures, the President of TopoTarget USA, John
Parsons Jr. has taken on the role of Chief Commercial Officer.
In Q3 2007 Savene™ revenues amounted to DKK 4.6 million compared to DKK 4.6
million in Q2 2007. This includes the expected seasonal effect of the European
summer vacation months of July and August and the all-time high sales figure of
DKK 1.9 million during September. Total sales of Savene™ for the first nine
months of 2007 amounted to DKK 12.9 million.
The figure below illustrates the quarterly Savene™ sales development, measured
in TDKK since its launch in October 2006.
In the attached pdf page 5 is a figure showing the quarterly development in
sales for Savene since launch in October 2006.
Medical provider groups in the US have expressed a high degree of desire to
include Totect™ in the treatment protocols for anthracycline extravasation and
TopoTarget has received a large number of requests regarding availability and
education in the use of Totect™. The medical oncology physicians, oncology
nurses and oncology pharmacists have expressed their desire to update existing
extravasation guidelines to include Totect™ as the treatment for anthracycline
extravasations. These revisions are expected in the first half of 2008.
Further clinical activities
TopoTarget's clinical pipeline consists of nine product candidates including
belinostat as discussed above, covering a broad range of cancer and other
indi-cations.
The guidance on the following development programs is consistent with
previ-ously announced guidance unless otherwise specified below.
Baceca® - an HDACi for the treatment of Basal Cell Carcinoma (BCC)
TopoTarget currently conducts two randomised and blinded Phase II
proof-of-concept trials to investigate Baceca® alone, and in combination with
two differ-ent vitamin A-like compounds for the treatment of BCC. These trials
will enrol a total of approximately 100 patients.
Savicol™ - an HDACi for the treatment of Familial Adenomatous Poly-posis (FAP)
TopoTarget is currently conducting a Phase II pivotal trial, evaluating the
effect of Savicol™ in the treatment of FAP. This randomised, placebo-controlled
Phase II study takes place in Europe and is expected to enrol a total of 60 FAP
pa-tients.
APO866 - an NAD+ inhibitor for the treatment of cancer
TopoTarget continues development of APO866, a specific inhibitor of the key
enzyme involved in the synthesis of NAD+, in three cancer trials. Treatment of
patients is ongoing in two Phase II clinical trials in advanced melanoma and
cutaneous T-Cell Lymphoma (CTCL), and in a phase I/II clinical trial in B-Cell
Lymphatic Leukaemia (B-CLL).
In addition, APO866 was selected by Windhover Information as one of the 10 most
interesting oncology products available for partnering. TopoTarget pre-sented
information regarding APO866 at Windhover' Information's Therapeutic Area
Partnerships meeting on 24-26 October 2007 in Philadelphia.
APO010 - a human FasLigand protein for the treatment of cancer
A Phase I dose-escalation study in patients with solid tumours is ongoing using
APO010 to determine an appropriate dose for use in Phase II clinical studies.
APO010 is a recombinant fusion protein product that targets Fas receptors on
the surface of cancer cells, and was generated using Apoxis' proprietary
MegaLigand technology.
Zemab® - an antibody-toxin for the treatment of HER2 positive cancers (i.e.
head & neck and breast cancer)
One Phase I trial has been completed. Following a new production of Zemab®, new
clinical studies are expected to be initiated in 2008. Zemab® benefits from the
new protein manufacturing expertise brought in-house with the acquisition of
Apoxis S.A.
Topotect - a topoisomerase II inhibitor - a protectant to enable chemo-therapy
treatment of brain metastasis
The potential of the combination of Topotect and etoposide is explored.
Recruitment of patients has been slow in this rare subset of metastasis
patients.
Avugane™ - an HDACi for the treatment of acne vulgaris
Based on Phase II proof-of-concept results showing comparable efficacy and
advantageous tolerability compared with a standard, marketed retinoid therapy,
TopoTarget now conducts a double-blind, randomised, placebo controlled Phase
clinical trial in mild to moderate acne vulgaris.
Conference call
TopoTarget will host a conference call this afternoon, 7 November, at 15.00
(CET), where management will present and discuss the results for the first nine
months of 2007.
A PowerPoint presentation will be available at TopoTarget's website,
www.topotarget.com (under Investor and Media > Presentations and Events),
before the start of the conference call.
To participate in the conference call please dial:
From Denmark: 70 26 50 40
Outside Denmark: +45 70 26 50 40 or +44 208 817 9301
The conference call will be held in English.
A replay will be available two hours after the conference call and until 14
November 2007 at the following number: +353 1 436 4267, security code 1072902#.
TopoTarget A/S
See page 8 in attached pdf for "highlights and key figures"
The financial ratios have been calculated in accordance with “Recommendations &
Ratios 2005”, issued by the Danish Society of Financial Analysts.
The interim financial statements are unaudited.
More detailed accounting information is provided in the appendices.
Comments on the interim financial statements for the nine months ended 30
September 2007
The company generated revenue of DKK 34.5 million during the period 1 Janu-ary
to 30 September 2007 compared with DKK 21.3 million in the same period of last
year. Included in revenues are invoicing to CuraGen and Savene™ sales. The
higher revenue in 2007 is mainly due to sales of Savene™ on various Euro-pean
markets.
In the first nine months of 2007, production costs amounted to DKK 19.7 million
as compared with DKK 13.8 million in the same period of 2006. The higher costs
were mainly due to increasing Savene™ sales in Europe.
The company's third-quarter revenue and production costs were lower than during
the first six months of 2007 because of slightly higher belinostat produc-tion
for clinical trials in the first half-year.
In the period 1 January to 30 September 2007, research and development costs
amounted to DKK 98.4 million as compared with DKK 86.8 million in the
year-earlier period. The increase in the company's research and development
costs were mainly due to the fact that TopoTarget Switzerland S.A. (previously
Apoxis S.A.) is included for the entire third quarter of 2007 following the
acquisition on 27 June 2007.
Sales and distribution costs amounted to DKK 39.7 million in the first nine
months, up from DKK 17.4 million in the same period of 2006. The higher costs
were mainly due to a higher number of sales staff in Europe because Savene™ is
being launched in more countries, and also because the company has estab-lished
a sales force in TopoTarget USA Inc. with a view to launching Totect™ in
October 2007. Marketing activities have thus been scaled up in the US.
In the period 1 January to 30 September 2007, administrative expenses amounted
to DKK 37.6 million as compared with DKK 31.6 million in the year-earlier
period. The increase was mainly due to an expansion in activities in TopoTarget
USA, Inc. and TopoTarget Switzerland S.A.
Net financial income amounted to DKK 4.4 million in the first nine months, as
compared with DKK 3.8 million in the year-earlier period. The increase was
mainly due to higher interest income on securities.
In the first nine months of 2007, tax amounted to an income of DKK 1.2 million
as compared with DKK 1.7 million in the same period of 2006. The tax income in
the first nine months of 2007 was due to a reduction of deferred tax liability
concerning TopoTarget Switzerland S.A., while the tax income in 2006 was due to
a reduction in deferred tax liability concerning TopoTarget Germany AG.
In the period 1 January to 30 September 2007, the company recorded a loss after
tax of DKK 155.3 million as compared with a loss after tax of DKK 122.8 million
in the same period of 2006.
At 30 September 2007, total assets amounted to DKK 823.5 million. Of this
amount, cash bank deposits and short-term securities amounted to DKK 463.1
million.
At 30 September 2007, equity amounted to DKK 673.8 million compared with DKK
312.7 million at the same time in 2006. The change consists of a loss of DKK
207.2 million during the period from 1 October 2006 to 30 September 2007, the
capital increases in November 2006 and June 2007 of DKK 121.7 million and DKK
332.0 million, respectively, additions during the period of share-based payment
totalling DKK 5.8 million, the exercise of warrants total-ling DKK 0.5 million
and fair value adjustment of the bond portfolio totalling DKK 0.4 million. Also
included is the net capital increase in connection with the acquisition of
Apoxis S.A. in the amount of DKK 107.9 million.
Outlook for 2007
On 27 June 2007, the company completed the acquisition of Apoxis S.A., which
will increase the Group's combined costs for activities such as clinical
trials. In October 2007, Totect™ was launched in the US market.
Pre tax loss guidance is changed to a range of DKK 255-275 million compared to
guidance on pre tax loss given in H1 2007 of DKK 275-295 million, primarily due
to positive synergies resulting from the integration of Apoxis S.A.
Statement by the Board of Directors and Senior Management
The Board of Directors and the Senior Management today discussed and adopted
the interim report for the nine months ended 30 September 2007.
The interim report, which is unaudited, is presented in accordance with IAS 34
and additional Danish disclosure requirements on the presentation of interim
reports by listed companies.
We consider the accounting policies to be appropriate, the accounting estimates
reasonable and the overall presentation of the interim report to be appropriate
to the effect that the interim report gives a true and fair view of the Group's
assets and liabilities, financial position, results of operations and cash
flows for the nine months ended 30 September 2007.
Copenhagen, 7 November 2007
Senior Management
Peter Buhl Jensen
CEO
Board of Directors
Håkan Åström Jesper Zeuthen Jeffrey Buchalter
Chairman
Anders Gersel Pedersen Ingelise Saunders Torbjørn Bjerke
Peter Buhl Jensen
For further information, please contact:
Dr. Peter Buhl Jensen Telephone +45 39 17 83 41
Chief Executive Officer Mobile +45 21 60 89 22
Tim Corcoran Telephone +44 1235 443 713
Chief Operating Officer Mobile +44 787 656 1027
Background information
About TopoTarget
TopoTarget (OMX: TOPO) is a biotech company, headquartered in Denmark and with
subsidiaries in US, Switzerland, Germany and the UK, dedicated to finding
''Answers for cancer'' and developing improved cancer therapies. TopoTarget is
founded and run by clinical cancer specialists and combines years of hands-on
clinical experience with in-depth understanding of the molecular mechanisms of
cancer. Focus lies on highly predic-tive cancer models and key cancer targets
(including HDACi, NAD+, mTOR, FasLigand and topoisomerase II inhibitors) and a
strong development foundation has been built. Topo-Target has a broad portfolio
of small molecule pre-clinical drug candidates and nine drugs (both small
molecules and protein based) are in clinical development, including both novel
anti-cancer therapeutics and new cancer indications for existing drugs.
Savene™/Totect™ was approved by EMEA in 2006 and the FDA in 2007 and is
TopoTarget's first product on the market. For more information, please refer to
www.topotarget.com.
TopoTarget Safe Harbour Statement
This announcement may contain forward-looking statements, including statements
about our expectations of the progression of our preclinical and clinical
pipeline including the timing for commencement and completion of clinical
trials and with respect to cash burn guidance. Such statements are based on
management's current expectations and are subject to a number of risks and
uncertainties that could cause actual results to differ materially from those
described in the forward-looking statements. TopoTarget cautions investors
that there can be no assurance that actual results or business conditions will
not differ materially from those projected or suggested in such forward-looking
statements as a result of various factors, including, but not limited to, the
following: the risk that any one or more of the drug development programs of
TopoTarget will not proceed as planned for technical, scientific or commercial
reasons or due to patient enrolment issues or based on new information from
non-clinical or clinical studies or from other sources; the success of
competing products and technologies; technological uncertainty and product
develop-ment risks; uncertainty of additional funding; TopoTarget's history of
incurring losses and the uncertainty of achieving profitability; TopoTarget's
stage of development as a bio-pharmaceutical company; government regulation;
patent infringement claims against TopoTarget's products, processes and
technologies; the ability to protect TopoTarget's patents and proprietary
rights; uncertainties relating to commercialization rights; and product
liability expo-sure; We disclaim any intention or obligation to update or
revise any forward-looking statements, whether as a result of new information,
future events, or otherwise, unless required by law.
